“Pro-aging factor” tied to immune-related molecule

“Pro-aging factor” tied to immune-related molecule

Aging process could result in cognitive impairment and increase the risks of developing neurodegenerative disorders during old age. In 2014, a highly publicized work on parabiosis, a process connecting circulatory system of a young mouse to an old mouse, showed that this method effectively reverses the declines in learning ability which typically emerged as mice age.

The key researchers involved in this study, Tony Wyss-Coray and Saul A Villeda, continue to explore the molecular differences between young and old blood. Published in Nature Medicine July 2015, their research showed that the level of a blood-borne molecule, beta-2 microglobulin (B2M), increases as we age. B2M belongs to one of the components of MHC Class I molecule, which traditionally been shown to present non-self antigens to immune cells such as the Cytotoxic T cells. Over the course of their long term study, the researchers have noted that blood from older animals seem to contain “pro-aging factor” that suppress neurogenesis, which in turn lead to cognitive impairment.

They first showed that B2M level rose with age in blood and the cerebrospinal fluid (CSF) in brain. When B2M is administered through circulatory system or directly into the CSF, young mice performed badly on learning and memory test compared to control mice. Through the immunostaining of brain with neurogenesis markers, they also found that the B2M-administered young mice have less events of neurogenesis as compared to their littermates. In contrary, when B2M is ablated, the old mice performed better than their WT counterparts on learning and memory tests, and the event of neurogenesis remain active in the brains of these mice even during old age.

The molecular mechanism of how B2M affects neurogenesis is still unclear. However, from a translational perspective, developing molecules to target this protein would be a good option to treat cognitive defects or neurodegenerative disorders in old age.